PROJECT SUMMARY Liver cancer is a major contributor to cancer mortality and has major racial disparities in incidence, with Hispanics, Asians, and Blacks all having significantly higher incidence than Whites. Survival rates for liver cancer are among the worst across all primary sites, and there has been little improvement over time. Therefore, investigating pathways to prevent liver cancer is likely the best approach to reduce its burden. Hepatocellular carcinoma (HCC) comprises the majority of all liver cancer cases. The biological pathways underlying the development of HCC are fairly well understood, with chronic liver injury leading to cirrhosis and oncogenic mutations. There are multiple types of liver injury which can lead to HCC, but the major pathways include hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease, typically secondary to type 2 diabetes and obesity. All of these pathways are preventable or modifiable, yet liver cancer rates continue to rise. Furthermore, these pathways do not explain why there are observed racial disparities in liver cancer. Past studies in breast and colorectal cancer have shown that racial residential segregation can increase the risk for incidence and decrease survival. Segregation is believed to play a role by increasing exposure to environmental risk factors or by limiting the socioeconomic status and health care access of affected communities. Despite the strong racial disparities in liver cancer, previous work has not investigated a potential link between racial segregation and liver cancer. The goal of this fellowship is to test the hypothesis that racial residential segregation is related to the development of, and mortality from, hepatocellular carcinoma. This will be achieved via three aims. In Aim 1, a novel local spatial index of segregation will be developed by using transportation data. For Aim 2, the potential relationship between this segregation index and the mortality rate of HCC will be investigated via regression analyses. Finally, Aim 3 will test if segregation affects an individual?s risk of developing HCC, once they already have acquired a liver disease or hepatitis. This shall be investigated by using a retrospective cohort of patients with liver disease or hepatitis and monitoring if and when they develop HCC. Through these three aims, the potential relationship between segregation and HCC shall be examined at both the beginning and end of HCC. This fellowship will result in novel methods and identify new relationships and epidemiological patterns that can help to target future efforts to reduce the burden of HCC.